Effect of niridazole in cellular immunity in vivo and in vitro

The Journal of Immunology

Administration of the antischistosomal compound niridazole to mice, guinea pigs, and humans results in the suppression of several manifestations of cell-mediated immunity. Sera from animals treated with niridazole blocked the in vitro production of migration inhibitory factor (MIF) while niridazole itself was inactive, suggesting that these effects are caused by water soluble mediators. We now report that crude extracts prepared from the urine of rats and a patient receiving niridazole, but not from pretreatment control urine, similarly suppress antigen-induced inhibition of migration of peritoneal exudate cells from sensitized guinea pigs. With immunosuppressive activity monitored by the direct MIF assay, combined solvent extraction and chromatographic techniques were used to fractionate immunosuppressive activity from the urine of niridazole-treated rats and the patient; the most active fractions, purified about 100- to 1000-fold as compared to methanol-water extracts of dried voi...

Journal of the American Association for Laboratory Animal Science : JAALAS, 2009

Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marr...

Transplantation Journal, 2014

Current immunosuppression regimens for solid-organ transplantation have shown disappointing efficacy in the prevention of chronic allograft rejection and carry unacceptable risks including toxicity, neoplasia, and lifethreatening infection. Achievement of immunological tolerance (long-term antigen unresponsiveness in an immunocompetent host) presents the exciting prospect of freedom from immunosuppression for transplant recipients. It is now 60 years since the first demonstration of immunological tolerance in animal models of transplantation, but translation into routine clinical practice remains elusive. Helminth parasites may provide novel strategies toward achieving this goal. Helminths are remarkably successful parasites: they currently infect more than one quarter of the world's population. It is now well established that the parasites' success is the result of active immunomodulation of their hosts' immune response. Although this primarily secures ongoing survival of the parasites, helminth-induced immunomodulation can also have a number of benefits for the host. Significant reductions in the prevalence of allergy and autoimmune conditions among helminth-infected populations are well recognized and there is now a significant body of evidence to suggest that harmful immune responses to alloantigens may be abrogated as well.

Plos Neglected Tropical Diseases, 2014

Background: It has been hypothesized that helminth infections increase HIV susceptibility by enhancing systemic immune activation and hence contribute to elevated HIV-1 transmission in sub-Saharan Africa. Objective: To study systemic immune activation and HIV-1 co-receptor expression in relation to different helminth infections and in response to helminth treatment. Methods: HIV-negative adults with (n = 189) or without (n = 57) different helminth infections, as diagnosed by Kato-Katz, were enrolled in Mbeya, Tanzania. Blinded to helminth infection status, T cell differentiation (CD45RO, CD27), activation (HLA-DR, CD38) and CCR5 expression was determined at baseline and 3 months after Albendazole/Praziquantel treatment. Plasma cytokine levels were compared using a cytometric bead array. Results: Trichuris and Ascaris infections were linked to increased frequencies of ''activated'' CD4 and/or CD8 T cells (p, 0.05), whereas Hookworm infection was associated with a trend towards decreased HLA-DR + CD8 T cell frequencies (p = 0.222). In Trichuris infected subjects, there was a linear correlation between HLA-DR + CD4 T cell frequencies and the cytokines IL-1b and IL-10 (p,0.05). Helminth treatment with Albendazole and Praziquantel significantly decreased eosinophilia for S. mansoni and Hookworm infections (p,0.005) but not for Trichuris infection and only moderately modulated T cell activation. CCR5 surface density on memory CD4 T cells was increased by 1.2-fold during Trichuris infection (p-value: 0.053) and reduced after treatment (p = 0.003). Conclusions: Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment.

British Journal of Pharmacology, 2001

Sulphamethoxazole has been associated with the occurrence of hypersensitivity reactions. There is controversy as to whether the immune response is metabolism-dependent or-independent. We have therefore investigated the site of antigen formation and the nature of the drug signal presented to the immune system in vivo. 2 Male Wistar rats were dosed with sulphamethoxazole, sulphamethoxazole hydroxylamine or nitroso sulphamethoxazole. Antigen formation on cell surfaces was determined by¯ow cytometry using a speci®c anti-sulphamethoxazole antibody. Immunogenicity was determined by assessment of ex vivo T-cell proliferation. 3 Administration of nitroso sulphamethoxazole, but not sulphamethoxazole or sulphamethoxazole hydroxylamine, resulted in antigen formation on the surface of lymphocytes, splenocytes and epidermal keratinocytes, and a strong proliferative response of splenocytes on re-stimulation with nitroso sulphamethoxazole. Rats dosed with sulphamethoxazole or sulphamethoxazole hydroxylamine did not respond to any of the test compounds. 4 CD4 + or CD8 + depleted cells responded equally to nitroso sulphamethoxazole. The proliferative response to nitroso sulphamethoxazole was seen even after pulsing for only 5 min, and was not inhibited by glutathione. Responding cells produced IFN-g, but not IL-4. 5 Haptenation of cells by sulphamethoxazole hydroxylamine was seen after depletion of glutathione by pre-treating the rats with diethyl maleate. Splenocytes from the glutathione-depleted sulphamethoxazole hydroxylamine-treated rats responded weakly to nitroso sulphamethoxazole, but not to sulphamethoxazole or sulphamethoxazole hydroxylamine. 6 Dosing of rats with sulphamethoxazole produced a cellular response to nitroso sulphamethoxazole (but not to sulphamethoxazole or its hydroxylamine) when the animals were primed with complete Freund's adjuvant. 7 These studies demonstrate the antigenicity of nitroso sulphamethoxazole in vivo and provide evidence for the role of drug metabolism and cell surface haptenation in the induction of a cellular immune response in the rat.

Mansoura Veterinary Medical Journal, 2021

Correspondence to: Eman Mohammed; Tel: +201099443698; Email: alfy79@gmail.com emanel Objective: The present study aims to investigate the possible adverse effects of the subcutaneous injection of nitroxynil and oral administration of albendazole in rabbits. Design: Randomized controlled experimental study. Animals: 18 New Zealand rabbits of 1.50 ± 0.5 kg body weight, were allocated randomly into three groups (n=6). Procedures: Group A served as control, the group B was treated with albendazole (20 mg /kg B. wt.) orally and the group C was treated with nitroxynil (10mg /kg B. wt.) subcutaneously. Blood samples were collected at 1, 7 and 14 days post drugs administration for hematological and biochemical determination. In addition, histopathological examination of liver, kidney and intestine specimens were performed. Results: The obtained results evoked a significant decrease in RBCs, PCV, Hb, WBCs, lymphocytes , neutrophils, GSH and catalase values in group B and C compared with that...

International Immunopharmacology, 2018

Metacestode (larval) stages of zoonotic cestodes of medical and veterinary importance cause chronic infections associated with immunosuppression. During mouse model of cestode infection induced by larvae of Mesocestoides (M.) vogae, we investigated the effects of dialyzable leukocyte extract (DLE) containing low-molecular weight substances (under 10 kDa) prepared from peripheral blood leukocytes of healthy human donors (available under commercial name IMMODIN). In the experiment, the effects of DLE as adjuvant to anthelmintic albendazole (ABZ) as well ABZ mono-therapy were also investigated. We showed that DLE enhanced therapeutic effect of ABZ by significant reduction of parasites number in both biased sites. Furthermore, administration of DLE reduced fibrosis and concentrations of lipid peroxides in the liver and thereby showed cytoprotective effect. In contrast, higher hydroxyproline level and numbers of larvae enclosed in fibrous capsules were found in ABZtreated group. In order to investigate whether DLE could affect parasite-induced immunosuppression, we evaluated selected immune parameters. The results showed that DLE administration to mice increased proliferation of concanavalin A stimulated splenic cells ex vivo. Similarly, in vitro study confirmed that DLE ameliorated hypo-responsiveness of T lymphocytes and partially reverted suppressive effect of parasites excretorysecretory products. In addition, flow cytometric analysis revealed higher numbers of T helper and NK cells in the spleen and peritoneal cavity of infected mice after DLE + ABZ therapy. We also found strongly reduced serum levels of TGF-β1 and IL-17 as well as modulation of cytokines associated with Th1/Th2 immunity. These results suggest that IMMODIN could serve as a suitable adjuvant to the primary anthelmintic therapy.

Cancer research, 1974

Imidazole-4-carboxamide, 5-(3,3-dimethyl-l-triazeno), NSC 45388 (DTIC), was administered for 5 consecutive days as a rapid 150-mg/sq m or 250-mg/sq m infusion to 13 patients with melanoma. DTIC did not interfere with induc tion of a cellular immune (delayed hypersensitivity) re sponse to dinitrochlorobenzene in 7 of 12 patients tested or with established delayed hypersensitivity reactions in 8 of 8 patients. The 5 nonresponders to dinitrochlorobenzene were unable to manifest a cellular immune response to skin test antigens even before treatment with DTIC. DTIC did not suppress the primary humoral response to Vi antigen in 7 of 12 patients. The secondary response to tetanus toxoid was normal in 5 of 7 patients. These results indicate that DTIC at these dosage schedules was only moderately immunosuppressive and inhibited humoral immune responses slightly more than the cellular responses tested.

Journal of the American Association for Laboratory Animal Science : JAALAS, 2008

Fenbendazole (FBZ) is an anthelmintic drug widely used to treat and prevent pinworm outbreaks in laboratory rodents. Although data in nonrodent species indicate possible effects of fenbendazole on the bone marrow and lymphocyte proliferation and function, little has been reported regarding possible effects on the rodent immune system. The purpose of the current study was to determine the effects of a therapeutic regimen of FBZ on immune parameters in BALB/c mice. Both 9-wk on-off and 5-wk continuous medicated feed protocols were assessed. No significant differences between normal and FBZ diet treated mice were observed in the following parameters: complete blood count, blood chemistry, quantitation of major T and B cell markers in spleen, quantitation of T cell markers in the thymus, spleen cell proliferation to T and B cell mitogens, bone marrow colony-forming cell assays, skin graft rejection, and primary and secondary humoral immune responses. These data indicate that FBZ treatme...

The Journal of Experimental Medicine, 1972

Cell-mediated cytotoxicity (CMC) in spleens and lymph nodes of allografted rats was determined by release of 51Cr from labeled target cells incubated with aggressor lymphoid cells. CMC was first detected in grafted adult rats on day 5, peaked on days 7 and 8, and declined rapidly to background levels by days 9 to 11. In allografted neonates and in cyclophosphamide-treated or neonatally thymectomized adults CMC was a fraction of that observed in normal adult rats. Enhancing antibodies deferred in vivo peak activity of CMC in allografted neonates for 3–4 days, and blocked in vitro the action of aggressor lymphocytes by binding to target cells. Enhancing antibodies had no effect on the cytotoxicity of aggressor cells, but horse antibodies to rat thoracic duct cells inhibited in vitro CMC of aggressor cells.